Somatomedin is a group of polypeptide serum growth factors postulated to mediate the growth-promoting action of growth hormone. In addition to their growth hormone-dependence, somatomedins have the following general properties: Insulin-like activity, stimulation of cell proliferation, stimulation of sulfate uptake into cartilage, and transport in plasma bound to a large molecular weight carrier protein. A wealth of clinical information on human growth suggests that somatomedin mediates the growth-promoting action of growth hormone and the production of growth in Snell dwarf mice by partially pure somatomedin supports this. However, to conclusively establish that somatomedin mediates the growth promoting-action of growth hormone, pure somatomedins must be shown to stimulate growth in growth hormone-deficient animals. This proposal plans to isolate a large amount of pure somatomedins from Cohn fraction IV by first extensively purifying the large molecular weight somatomedin-carrier protein complex. A method developed in our lab yields the somatomedin-carrier protein complex at a specific activity of 0.7 U/mg. The somatomedins will be separated from the carrier protein and purified by the method of Rinderknecht and Humbel (1976). Since we shall be starting the Rinderknecht method with material with 100 times the specific activity previously used, we expect to have excellent overall yields. Individual and combined somatomedins will be injected into hypophysectomized rats and the effect on growth and growth-related parameters observed and compared to controls.